“Elucidating these regulatory mechanisms is of fundamental importance both for understanding cell behavior in normal conditions, and also why genes are not properly controlled in some diseases such as cancer”, says Mattias Mannervik, Professor at the Department of Molecular Biosciences, The Wenner Gren Institute, Stockholm University and corresponding author of the study.
Creation of different cell types from an identical DNA sequence is one of the most remarkable events in life. Every cell in our bodies contains the same genes, but whereas a skin cell uses one set of genes, a brain cell uses another set. This is largely controlled at a process called transcription, whereby the genes are copied (transcribed) into a messenger RNA that is translated into a protein. The enzyme that transcribes genes is called RNA polymerase II, and its activity is controlled by other proteins called transcription factors. Transcription factors rely on yet other proteins, co-regulators, to control RNA polymerase activity. Co-regulators include the enzymes p300 and CBP, which add so called acetyl groups to other proteins, including the histones that compact and pack the DNA molecule so that it fits in the tiny cell nucleus.
In the present study, the researchers have shown that CBP directly controls RNA polymerase II activity. Treating cells with a drug that inhibits CBP results in less binding of RNA polymerase II to DNA transcription start sites, and also leads to less efficient RNA polymerase II gene transcription due to defective histone acetylation. These effects are observed on virtually all active genes in these cells.
“Our research has revealed the mechanisms by which the transcription co-regulator CBP controls gene expression, which increases our understanding of normal cell physiology, and may help to explain why CBP is frequently altered in some human cancers”, says Mattias Mannervik.
The publication in a wider concept: Gene-Environment Interactions
MOVIE: Mattias Mannervik describes his research
Mattias Mannervik's research group at MBW
Read more in a press-release from Umeå University
Publication:
"CBP regulates recruitment and release of promoter-proximal RNA polymerase II"
Ann Boija, Dig Bijay Marat, Aman Zare, Per-Henrik Holmqvist, Philge Philip, David J. Meyers, Philip A. Cole, John T. Lis, Per Stenberg and Mattias Mannervik
Molecular Cell, Published online October 19, 2017
Contact Information:
Mattias Mannervik, PhD, Professor
Stockholm University
Department of Molecular Biosciences,
The Wenner-Gren Institute
SE-106 91 Stockholm
Telephone: +46 8 16 1565
E-mail: mattias.mannervik@su.se
